This Supplemental Grant Application proposes a clinical investigation of oxidative injury in autistic individuals. It will be a collaborative study with Bill Walsh, Chief Scientist at the Health Research Institute, and George Perry, Professor of Pathology at the Case Western Reserve University School of Medicine. There is ample presumptive evidence that oxidative injury and autoimmunity contribute to the etiopathology of this apparently multifactorial neurodevelopmental disorder. However, there is little direct evidence for oxidative injury in autistics. Therefore, confirmation of the hypothesis that oxidative injury is associated with autism would have a major impact on our understanding of the disease. The specific aims and immediate goals of the studies proposed in this supplemental grant application are: (1) to determine the extent to which oxidative injury, as measured by levels of lipid-derived oxidative protein modifications and autoantibodies in blood and brain tissue from autistic individuals, is elevated compared with healthy controls; and (2) to provide tools for measuring the efficacy of therapeutic treatments in reducing oxidative injury in autistic individuals. The broad long-term goals of the proposed new studies also include determining: (3) if levels of antioxidants, antioxidant enzymes, redox active metals, and metallothionene are correlated with oxidative injury in autistics; and (4) if the reduction of oxidative stress correlates with improvements in mental health. [unreadable] [unreadable] Our markers of lipid-derived oxidative protein modification have proven effective for the ELISA detection in blood of oxidative injury associated with cardiovascular disease, end-stage renal failure, and retinal disease. They have also been effective for immunocytochemical detection of oxidative injury in brain and retina tissue. Medical practitioners urged us to undertake the proposed new collaborative clinical studies. They invited us to expand our efforts to include their area of concern: the possible involvement of oxidative injury in brain disorders. The proposed expansion of the "Preprostaglandin Endoperoxides" project will provide an opportunity for productive new interactions with a group of clinicians who are committed to learning new ways to help their patients. Although we have had some successful past collaborations with George Perry examining oxidative injury in Alzheimer's and Alexander's diseased brain tissue, the proposed studies represent a major expansion of our involvement in brain disease-related research. [unreadable] [unreadable]